Interferon-?2a induces CD4+T cell apoptosis and suppresses Th1/Th17 responses via upregulating IRF1-mediated PDL1 expression in dendritic cells from Behcet?s uveitis

作者全名："Zhu, Yunyun; Yu, Qiuyue; Su, Guannan; Shao, Na; Feng, Jie; Luo, Xiang; Zhou, Chunjiang; Yang, Peizeng"

作者地址："[Zhu, Yunyun; Yu, Qiuyue; Su, Guannan; Luo, Xiang; Zhou, Chunjiang; Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Branch,Municipal Div Natl Clin Res Ctr O, Chongqing, Peoples R China; [Zhu, Yunyun; Shao, Na; Feng, Jie] Jining 1 Peoples Hosp, Dept Ophthalmol, Jining, Peoples R China; [Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000970194000001

JCR分区：Q1

影响因子：8.6

年份：2023

卷号：250

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Behcet?s uveitis; Interferon-?2a; PDL1; IRF1; Dendritic cells; CD4+T cells

摘要："Recombinant interferon-alpha 2a (IFN alpha 2a) has been widely used in the treatment of Behcet's uveitis (BU). However, the mechanism underlying its effects remains poorly understood. In this study, we investigated its effect on dendritic cells (DCs) and CD4+ T cells, which are essential for the development of BU. Our results showed that the expression of PDL1 and IRF1 was significantly decreased in DCs from active BU patients, and IFN alpha 2a could significantly upregulate PDL1 expression in an IRF1-dependent manner. IFN alpha 2a-treated DCs induced CD4+ T cells apoptosis and inhibited the Th1/Th17 immune response in association with reduced secretion of IFN-gamma and IL-17. We also found that IFN alpha 2a promoted Th1 cell differentiation and IL-10 secretion by CD4+ T cells. Finally, a comparison of patients before and after IFN alpha 2a therapy revealed that the frequencies of Th1/Th17 cells significantly decreased in association with remission of uveitis after IFN alpha 2a therapy. Collectively, these results show that IFN alpha 2a could exert its effects by modulating the function of DCs and CD4+ T cells in BU."

基金机构："National Natural Science Foundation Key Program [81930023, 82230032]; Chongqing Outstanding Science Project [2019]; Chongqing Chief Medical Scientist Project [2018]; Chongqing Key Laboratory of Ophthalmology [2008CA5003]; Chongqing Science & Technology Platform and Base Construction Program [cstc2014pt-sy10002]; Key Project of Chongqing Science and Technology Bureau [CSTC2021jscx-gksb-N0010]; Natural Science Foundation of Shandong [ZR2019PH093]"

基金资助正文："This work was supported by the National Natural Science Foundation Key Program [grant numbers 82230032] ; the National Natural Science Foundation Key Program [grant numbers 81930023] ; the Chongqing Outstanding Science Project [grant numbers 2019] ; the Chongqing Chief Medical Scientist Project [grant numbers 2018] ; the Chongqing Key Laboratory of Ophthalmology [grant numbers CSTC, 2008CA5003] ; the Chongqing Science & Technology Platform and Base Construction Program [grant numbers cstc2014pt-sy10002] ; the Key Project of Chongqing Science and Technology Bureau [grant numbers CSTC2021jscx-gksb-N0010] ; and the Natural Science Foundation of Shandong [grant numbers ZR2019PH093] . The funding sources had no role in the design or conduct of the study."